The main function of lungs is to transfer oxygen from the atmosphere into the blood and expel carbon dioxide therefrom to the atmosphere. For patients with diseased or damaged lungs, there are few options. Some of the most common diseases leading to end-stage lung failure include, inter alia, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). There are also many people suffering from lung cancer and poor lung function due to years of smoking who are not eligible for a lung resection or lung transplantation.
Lung transplantation remains the main therapy for chronic irreversible respiratory failure. However, only about 1,000 procedures are performed each year due to the severe shortage of suitable donor organs. See, e.g., Franco et al.: “Heart-Lung Transplantation for Cystic Fibrosis,” Journal of Applied Cardiology 4:571 (1989). The most common indications for lung transplantation include COPD, CF, IPF, and PH. Patients with lung cancer are not candidates for transplantation because the use of immunosuppression could potentially cause the cancer to spread. Lung transplant candidates can die waiting for an organ donor since the average waiting time period may exceed two years. The overall results are not ideal due to the extensive surgery required, deterioration of the patient's condition during the waiting period, the complications of chronic immunosuppression, infection, and the development of chronic rejection. Also, many patients with chronic lung disease tend to be older individuals who are poor candidates for transplantation because they do not tolerate immunosuppression.
Xenotransplantation has been explored as an option to solve the donor shortage, but success remains years away until the cross-species immunologic barriers can be completely overcome, see et al., Higgins et al.: “Improved Ultrastructural Lung Preservation with Prostaglandin El as Donor Pre-treatment in a Primate Heart-Lung Transplant Model”, JTHCVS 105:965 (1993). Advances in xenotransplantation are occurring but clinical trials are still in the future, and the first use of such organs would probably be closely related to the current human lung transplantation surgery. Although xenotransplantation would help with the donor shortage, it would not solve many of the other issues involved with human lung transplantation, such as immunosuppression.
Another option for patients suffering from diseased or damaged lungs may be to utilize an enriched oxygen supply, frequently in conjunction with a ventilator. However, this has been shown to create dependency and a host of other ventilator-related disorders. See e.g., Candadai et al., “Weaning success among ventilator-dependent patients in a rehabilitation facility”, Arch Phys Med Rehabil 2002; 83:154-7; Slutsky, A. S., “Lung Injury Caused by Mechanical Ventilation.” CHEST, vol. 116 no. suppl. 19S-15S, July 1999).
The concept of using an artificial lung in clinical medicine to take over the gas exchange function of diseased or damaged lung(s) dates back to the development of the heart-lung machine in 1954. Cardiopulmonary bypass (CPB) is a technique used to take over the function of the heart and lungs during surgery by regulating the circulation of blood and oxygen within a person's body. The artificial lung may provide short-term pulmonary support during extensive operations on the heart.
Over the last 20 years, several conventional mechanical-assisting devices have been developed to treat diseased or damaged lung(s) acute reversible respiratory failure due to acute respiratory distress syndrome (ARDS). Conventional systems have also been developed for short-term pulmonary support (e.g., days to a few weeks). These systems include extracorporeal membrane oxygenation (ECMO) devices, extracorporeal carbon dioxide removal (ECCO2R) devices, and intravascular oxygenators (IVOX) devices.
Although conventional ECMO and IVOX systems have been used for aiding patients with diseased or damaged lung(s), they are both one-stage systems with distinct drawbacks. ECMO devices produce significant complication rates and typically do not provide a significant improvement. IVOX devices may alleviate some of the problems associated with ECMO devices. However, the gas exchange area of IVOX devices may be too small and the device may not provide the needed total support for gas exchange. Also, IVOX devices may not take away excess carbon dioxide leftover within the system. ECCO2R and ECMO are also one-stage systems and may be limited by the inclusion of fibers that come in contact with blood thereby causing blood activation and thrombogenesis.
In the past decade, IVOX systems have been the primary focus for treating diseased or damaged lung(s). Conventional one-stage IVOX systems typically include membranous or fibrous components used for oxygenation. Typically, a bundle of hollow fibers may be used as the oxygenating element. Exposing blood to the large artificial surface area needed for gas exchange often causes blood activation and thrombogenesis.
There has also been some research in utilizing an oxygen-carrying liquid to bring oxygen directly to the blood, however this research has focused on using small bubbles of liquid that are injected into the blood and then removed using a selective filter. When bubbles of fluid are injected into the blood, the system typically requires a means for pulling the bubbles out of the blood before it flows back into a user, which may also cause blood activation. These systems typically do not appreciably decrease the amount of carbon dioxide in the blood.